Real-world effectiveness of airway clearance techniques in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is commonly characterised by thick respiratory mucus. From diagnosis, people with CF are prescribed daily physiotherapy, including airway clearance techniques (ACTs). ACTs consume a large proportion of treatment time, yet the efficacy and effectiveness of ACTs are poorly understood. This study aimed to evaluate associations between the quality and quantity of ACTs and lung function in children and young people with CF. METHODS: Project Fizzyo, a longitudinal observational cohort study in the UK, used remote monitoring with electronic pressure sensors attached to four different commercial ACT devices to record real-time, breath-by-breath pressure data during usual ACTs undertaken at home over 16 months in 145 children. ACTs were categorised either as conformant or not with current ACT recommendations based on breath pressure and length measurements, or as missed treatments if not recorded. Daily, weekly and monthly associations between ACT category and lung function were investigated using linear mixed effects regression models adjusting for clinical confounders. RESULTS: After exclusions, 45 224 ACT treatments (135 individuals) and 21 069 days without treatments (141 individuals) were analysed. The mean±sd age of participants was 10.2±2.9 years. Conformant ACTs (21%) had significantly higher forced expiratory volume in 1 s (FEV1) (mean effect size 0.23 (95% CI 0.19-0.27) FEV1 % pred per treatment) than non-conformant (79%) or missed treatments. There was no benefit from non-conformant or missed treatments and no significant difference in FEV1 between them (mean effect size 0.02 (95% CI -0.01-0.05) FEV1 % pred per treatment). CONCLUSIONS: ACTs are beneficial when performed as recommended, but most people use techniques that do not improve lung function. Work is needed to monitor and improve ACT quality and to increase the proportion of people doing effective airway clearance at home.

Exploring flexible polynomial regression as a method to align routine clinical outcomes with daily data capture through remote technologies.

BACKGROUND: Clinical outcomes are normally captured less frequently than data from remote technologies, leaving a disparity in volumes of data from these different sources. To align these data, flexible polynomial regression was investigated to estimate personalised trends for a continuous outcome over time. METHODS: Using electronic health records, flexible polynomial regression models inclusive of a 1st up to a 4th order were calculated to predict forced expiratory volume in 1 s (FEV1) over time in children with cystic fibrosis. The model with the lowest AIC for each individual was selected as the best fit. The optimal parameters for using flexible polynomials were investigated by comparing the measured FEV1 values to the values given by the individualised polynomial. RESULTS: There were 8,549 FEV1 measurements from 267 individuals. For individuals with > 15 measurements (n = 178), the polynomial predictions worked well; however, with < 15 measurements (n = 89), the polynomial models were conditional on the number of measurements and time between measurements. The method was validated using BMI in the same population of children. CONCLUSION: Flexible polynomials can be used to extrapolate clinical outcome measures at frequent time intervals to align with daily data captured through remote technologies.

Burns dressings.

BACKGROUND: Burn injuries are common and costly; each year, there are more than 200,000 cases, costing the Australian community $150 million. Management of smaller burn injuries in the community can be improved by appropriate first aid, good burn dressings and wound management. This can reduce the risk of the burn becoming deeper or infected, and can potentially reduce the requirement for specialist review or surgery. OBJECTIVE: The objective of this article is to provide healthcare professionals with information about the pathophysiology of burn wound progression. This information includes the aims of burn wound dressings and indications for different types of dressings in different burn depths, advantages of blister debridement, and the reasoning behind advice given to patients after healing of the burn wound. DISCUSSION: This article provides a framework used by the State Burn Service of Western Australia, by which clinicians can understand the needs of a specific burn wound and apply these principles when choosing an appropriate burn dressing for their patient. Every intervention in the journey of a patient with a burn injury affects their eventual outcome. By managing all burn injuries effectively at every single step, we can reduce burn injury morbidity as a community.

First do no harm: A patient-reported survey of split skin graft donor site morbidities following thin and super-thin graft harvest.

The split-thickness skin graft (STSG) donor site is the commonest used during burn surgery which has its own complications and as such the focus should be on minimizing it. Modifications to practice in our unit which we believe aid this include limiting the amount of STSG taken and the harvest of super-thin STSGs, with 0.003-0.005 in. (0.08-0.13 mm) being the commonest dermatome settings used. A patient-reported survey via a mobile phone link to a questionnaire was sent to 250 patients who had a STSG for an acute burn between 1st August 2020 and 31st July 2021. Patient demographics were collected from electronic records including the thickness of the FTSG taken when recorded. Patient responses were statistically analyzed and logistic regression with backwards elimination was performed to explore which contributing factors led to an improved experience of the donor site. Questionnaire responses were obtained from 107 patients (43%). These were between one and two and a half years after the injury. Concerning early donor site issues, itch was a problem for 52% of patients, pain was a problem for 48% of patients. Less common problems (fewer than 25% of patients) were leaking donor sites, wound breakdown, and over-granulation. Regarding long-term outcomes, increased, decreased or mixed pigmentation at the donor site was reported by 32% patients at the time of the survey. Hyper-vascular donor sites were reported by 24% patients. Raised or uneven feeling donor sites were reported by 19% patients, firm or stiff donor sites by 13% patients, and altered sensation by 10% patients. At the time of the survey, 70% responders reported their donor site looked "the same or about the same as my normal skin". Of these, 62 reported how long it took for this to happen, and it equates to a third looking normal at 6 months and half looking normal at a year. For the 32 patients who reported their donor site looking abnormal, 72% were "not bothered" by it. Patients with super-thin grafts (0.003-0.005 in.) were significantly more likely to have normal sensation, normal stiffness, and be less raised at their donor sites than those who had thin grafts (0.006-0.008 in.). This survey gives important information on patients' experiences of donor site morbidity that may form part of an informed consent process and allow tailored advice. Furthermore, it suggests that super-thin grafts may provide a superior donor site experience for patients.

Using reference equations to standardise incremental shuttle walk test performance in children and young people with chronic conditions and facilitate the evaluation of exercise capacity and disease severity.

AIMS: The aim was to evaluate whether standardised exercise performance during the incremental shuttle walk test (ISWT) can be used to assess disease severity in children and young people (CYP) with chronic conditions, through (1) identifying the most appropriate paediatric normative reference equation for the ISWT, (2) assessing how well CYP with haemophilia and cystic fibrosis (CF) perform against the values predicted by the best fit reference equation and (3) evaluating the association between standardised ISWT performance and disease severity. METHODS: A cross-sectional analysis was carried out using existing data from two independent studies (2018-2019) at paediatric hospitals in London,UK. CYP with haemophilia (n=35) and CF (n=134) aged 5-18 years were included. Published reference equations for standardising ISWT were evaluated through a comparison of populations, and Bland-Altman analysis was used to assess the level of agreement between distances predicted by each equation. Associations between ISWT and disease severity were assessed with linear regression. RESULTS: Three relevant reference equations were identified for the ISWT that standardised performance based on age, sex and body mass index (Vardhan, Lanza, Pinho). A systematic proportional bias of standardised ISWT was observed in all equations, most pronounced with Vardhan and Lanza; the male Pinho equation was identified as most appropriate. On average, CYP with CF and haemophilia performed worse than predicted by the Pihno equation, although the range was wide. Standardised ISWT, and not ISWT distance alone, was significantly associated with forced expiratory volume in 1 s in CYP with CF. Standardised ISWT in CYP with haemophilia was slightly associated with haemophilia joint health score, but this was not significant. CONCLUSIONS: ISWT performance may be useful in a clinic to identify those with worsening disease, but only when performance is standardised against a healthy reference population. The development of validated global reference equations is necessary for more robust assessment.

Carbon dioxide laser treatment of burn-related scarring: Results of the ELIPSE (Early Laser Intervention Promotes Scar Evolution) prospective randomized controlled trial.

AIM: To investigate the impact of ablative fractional carbon dioxide laser (AFCO2L) on patient-reported outcomes measures, subjective scar appearance, dermal architecture, and gene transcription in early burn scars. METHODS: Fifteen adult patients with a burn-related scar were recruited. Inclusion criteria were two non-contiguous scar areas of 1% total body surface area, similar baseline Vancouver scar scale (VSS) score and 3months since the time of injury. All participants acted as their own control. Scars were randomized to treatment or control. Treatment scars received three AFCO2L treatments at 6-week intervals. Outcome measures were recorded at baseline, 3, 6, and 12-months post-treatment. Measures included blinded VSS, Patient Observer Scar Assessment Scale (POSAS), Brisbane Burn Scar Impact Profile (BBSIP), blinded scar photo assessment, histological tissue analysis, and RNA sequencing analysis. RESULTS: No significant difference was found in VSS, scar erythema, or pigmentation. Patient POSAS improved in scar thickness and texture following AFCO2L. All elements of BBSIP improved in control and laser groups. AFCO2L-treated scars were scored better than control scars by blinded raters. RNA sequencing illustrated that AFCO2L induced sustained changes in fibroblast gene expression. CONCLUSIONS: AFCO2L treated scars had significantly altered scar thickness and texture 6 months post-laser and were rated better than controls on blinded photo analysis after 3 treatments. RNASeq results suggest laser treatment alters the transcriptome of treated fibroblasts for at least 3 months after treatment. Expansion of this research to study in more depth fibroblast changes in response to laser, as well as assessing the impact on daily activity and quality of life, will be beneficial.

Quantity and quality of airway clearance in children and young people with cystic fibrosis.

Children and young people with CF (CYPwCF) get advice about using positive expiratory pressure (PEP) or oscillating PEP (OPEP) devices to clear sticky mucus from their lungs. However, little is known about the quantity (number of treatments, breaths, or sets) or quality (breath pressures and lengths) of these daily airway clearance techniques (ACTs) undertaken at home. This study used electronic pressure sensors to record real time breath-by-breath data from 145 CYPwCF (6-16y) during routine ACTs over 2 months. ACT quantity and quality were benchmarked against individual prescriptions and accepted recommendations for device use. In total 742,084 breaths from 9,081 treatments were recorded. Individual CYPwCF maintained consistent patterns of ACT quantity and quality over time. Overall, 60% of CYPwCF did at least half their prescribed treatments, while 27% did fewer than a quarter. About 77% of pre-teens did the right number of daily treatments compared with only 56% of teenagers. CYPwCF usually did the right number of breaths. ACT quality (recommended breath length and pressure) varied between participants and depended on device. Breath pressures, lengths and pressure-length relationships were significantly different between ACT devices. PEP devices encouraged longer breaths with lower pressures, while OPEP devices encouraged shorter breaths with higher pressures. More breaths per treatment were within advised ranges for both pressure and length using PEP (30-31%) than OPEP devices (1-3%). Objective measures of quantity and quality may help to optimise ACT device selection and support CYPwCF to do regular effective ACTs.

The impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review.

BACKGROUND: Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF. METHODS: A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity. DISCUSSION: This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020184411.

Protocol for Project Fizzyo, an analytic longitudinal observational cohort study of physiotherapy for children and young people with cystic fibrosis, with interrupted time-series design.

INTRODUCTION: Daily physiotherapy is believed to mitigate the progression of cystic fibrosis (CF) lung disease. However, physiotherapy airway clearance techniques (ACTs) are burdensome and the evidence guiding practice remains weak. This paper describes the protocol for Project Fizzyo, which uses innovative technology and analysis methods to remotely capture longitudinal daily data from physiotherapy treatments to measure adherence and prospectively evaluate associations with clinical outcomes. METHODS AND ANALYSIS: A cohort of 145 children and young people with CF aged 6-16 years were recruited. Each participant will record their usual physiotherapy sessions daily for 16 months, using remote monitoring sensors: (1) a bespoke ACT sensor, inserted into their usual ACT device and (2) a Fitbit Alta HR activity tracker. Real-time breath pressure during ACTs, and heart rate and daily step counts (Fitbit) are synced using specific software applications. An interrupted time-series design will facilitate evaluation of ACT interventions (feedback and ACT-driven gaming). Baseline, mid and endpoint assessments of spirometry, exercise capacity and quality of life and longitudinal clinical record data will also be collected.This large dataset will be analysed in R using big data analytics approaches. Distinct ACT and physical activity adherence profiles will be identified, using cluster analysis to define groups of individuals based on measured characteristics and any relationships to clinical profiles assessed. Changes in adherence to physiotherapy over time or in relation to ACT interventions will be quantified and evaluated in relation to clinical outcomes. ETHICS AND DISSEMINATION: Ethical approval for this study (IRAS: 228625) was granted by the London-Brighton and Sussex NREC (18/LO/1038). Findings will be disseminated via peer-reviewed publications, at conferences and via CF clinical networks. The statistical code will be published in the Fizzyo GitHub repository and the dataset stored in the Great Ormond Street Hospital Digital Research Environment. TRIAL REGISTRATION NUMBER: ISRCTN51624752; Pre-results.

Effectiveness and safety of perioperative enteral feeding in patients with burn injuries: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine whether perioperative enteral feeding improves outcomes in patients with burns. INTRODUCTION: Literature has identified many positive benefits of nutrition support for patients with burn injuries, including preservation of lean body mass, improved wound healing, reduced gastrointestinal permeability and enhanced immunity. Fasting for surgery can undermine the nutritional care of these patients by causing nutrient deficits. It may also negatively affect patient well-being and insulin resistance. Perioperative fasting is intended to protect patients from regurgitation and pulmonary aspiration. This research aims to investigate whether perioperative feeding impacts outcomes in patients with burn injuries. INCLUSION CRITERIA: This systematic review will consider studies whose participants have a burn injury. The intervention is perioperative enteral feeding (either intragastric or post-pyloric). Patients who received perioperative feeding will be compared with patients who had enteral nutrition withheld during the perioperative period. A number of outcome measures will be investigated, including mortality, length of stay, wound infection, wound healing rate and aspiration pneumonia. METHODS: The key databases searched will be PubMed, CINAHL, Embase, Web of Science and Cochrane Central Register of Controlled Trials and Scopus. Only studies published in English will be considered. There will be no date limits. Full texts of selected studies will be retrieved and assessed against inclusion criteria. Studies that do not meet the inclusion criteria will be excluded, with reasons provided. Data synthesis will be pooled in a statistical meta-analysis. Subgroup analysis will be conducted where possible. Where statistical pooling is not possible, the findings will be presented in narrative form. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018119034.

Carbon dioxide laser treatment in burn-related scarring: A prospective randomised controlled trial.

AIM: To investigate the effect of ablative fractional CO2 laser (AFCO2L) on burns scar appearance and dermal architecture at 6 weeks and up to 3-years post-treatment. METHODS: Twenty adult patients with a burn-related scar were recruited. Inclusion criteria were a minimum scar area of 10 × 10 cm and Vancouver scar scale (VSS) score of >5 and ≥6 months since the time of injury. The region of scar was randomised to treatment/control zones. Treatment zones received 3 standardised laser treatments at 4- to 6-week intervals. All areas of scar received standard scar care. Outcome measures were recorded at baseline, 6-weeks post final treatment and up to 3 years post-treatment. Measures included blinded assessor VSS, Patient Scar Assessment Scale and histological tissue analysis. RESULTS: Nineteen and nine patients completed the short- and long-term studies, respectively. Clinical results revealed improvement in all scar areas over time. There was a statistically significant improvement in pain and itch in the treatment zone compared to the control zone at 6 weeks. Histological data revealed a significant increase in medium-sized collagen fibres at 6 weeks relative to the control site. Sub-group analysis according to scar age revealed greater histological improvement following laser treatment in immature scars relative to more mature scar. CONCLUSIONS: Results demonstrate that 3 treatments of AFCO2L significantly improve scar pain, itch and dermal architecture at 6 weeks post-treatment. Histological results suggest greater potential in treating immature scar. Further investigation into the timing of laser treatment could help assist treatment protocols.

Chondrosarcomatous Differentiation in a Large Malignant Melanoma of the Scalp.

Background. Divergent differentiation in malignant melanoma is a rare phenomenon, which can lead to delayed diagnosis or misdiagnosis, impacting upon patient treatment and outcome, as well as the understanding of tumour behaviour. Case. We present the case of a large long-standing tumour on the scalp of a 72-year-old female patient, which when excised and examined histologically was revealed to be a nodular malignant melanoma displaying chondrosarcomatous differentiation. Foci suggestive of lentigo maligna were also present. Rapid metastatic spread of the tumour was observed shortly after the primary resection. Discussion. To our knowledge, this is the first reported case in the literature of chondrosarcomatous differentiation in a lentigo maligna melanoma. The clinical and histopathological details and images of this case are presented alongside a discussion regarding such tumours and patterns of similar tumour behaviour.

Using frozen section margin control technique to manage non-melanomatous skin lesions in high-risk sites.

BACKGROUND: In the UK, non-melanoma skin cancers (NMSCs) that are incompletely excised, recurrent or in sites high risk for incomplete excision are often offered Mohs micrographic surgery (MMS). Variations in waiting times and geographical access to MMS affect patient preference for other treatments. Our unit offers excision of such lesions under complete margin frozen section histological examination. METHODS: All NMSCs excised at our unit by complete margin frozen section histological analysis from 2010 to 2014 were retrospectively reviewed. The number of excisions required, complete excision rates and recurrences to date were analysed. RESULTS: Sixty-nine patients were treated using this technique with a total of 70 lesions excised. Approximately 71% of the excision margins were clear after primary excision, 27% at second excision and 1% at third excision. Patients had a mean follow-up of 12 months (range: 1-48) with no patients lost to follow-up and no recurrences reported to date. Ninety-eight percent of NMSC cases were completely excised and two cases were incompletely excised. CONCLUSION: We have found the rates of excision and recurrence of the high-risk NMSCs excised at our unit to be comparable to those reported with MMS. In addition, our data show that around 29% of patients would have had incomplete margins on primary resection, thus justifying the use of this technique in this group. We suggest that this technique is a safe and useful alternative to MMS in areas where waiting times or geographical patient preference may prohibit its use.

Comparison of mortality prediction models in burns ICU patients in Pinderfields Hospital over 3 years.

BACKGROUND: Many different burns mortality prediction models exist; however most agree that important factors that can be weighted include the age of the patient, the total percentage of body surface area burned and the presence or absence of smoke inhalation. METHODS: A retrospective review of all burns primarily admitted to Pinderfields Burns ICU under joint care of burns surgeons and intensivists for the past 3 years was completed. Predicted mortality was calculated using the revised Baux score (2010), the Belgian Outcome in Burn Injury score (2009) and the Boston group score by Ryan et al. (1998). Additionally 28 of the 48 patients had APACHE II scores recorded on admission and the predicted and actual mortality of this group were compared. RESULTS: The Belgian score had the highest sensitivity and negative predictive value (72%/85%); followed by the Boston score (66%/78%) and then the revised Baux score (53%/70%). APACHE II scores had higher sensitivity (81%) and NPV (92%) than any of the burns scores. DISCUSSION: In our group of burns ICU patients the Belgian model was the most sensitive and specific predictor of mortality. In our subgroup of patients with APACHE II data, this score more accurately predicted survival and mortality.

Effects of perforator number and location on the total pedicle flow and perfusion of zone IV skin and fat of DIEP flaps.

BACKGROUND: DIEP flaps are a popular choice for autologous breast reconstruction, though many surgeons routinely discard zone IV, limiting transferrable tissue. We investigated the effect of altering number and location of perforators supplying the flap on total pedicle flow and perfusion of skin and fat of zone IV. METHODS: 20 cranially-based abdominal epigastric perforator flaps were raised in rats on two perforators. The perforators were sequentially clamped and released in a randomised order and total pedicle flow measured using microvascular flow-probes, on the following perforator combinations: 13 DIEP flaps were raised in post-mastectomy patients requiring breast reconstruction on two perforators. These were clamped and released as before to assess perfusion of fat and skin in zone IV using SPY indocyanine-green-fluorescence-angiography scans on the same perforator combinations as in our animal study, listed above. RESULTS: All data were analysed using 2-way-ANOVA and revealed that vascular flow was significantly (p < 0.0001) greater on one perforator as opposed to two. These results were supported by our human study, revealing both zone IV fat and skin perfusion were significantly (p < 0.0001) greater when a single perforator was used. CONCLUSIONS: Our data suggests total pedicle flow and perfusion of zone IV fat and skin is significantly higher on a single perforating blood vessel as opposed to two. Reasons for these observed differences could be due to changing pressure gradients across a piece of tissue prone to venous congestion, with maintenance of flow better in a single lumen.